The macula is the central part of the retina responsible for the majority of central vision. It is comprised of the fovea, a small, cone-dominated region, which is surrounded by the rod-dominated parafovea. Photoreceptor density decreases extending out from the macula, with an almost complete loss of cone receptors outside of the inner ten degrees.
Photoreceptors are dependent on the health of the Retinal Pigment Epithelium (RPE) and Bruch's membrane complex. This complex is responsible for nutrient and waste exchange, keeping the photoreceptors healthy and clearing substances such as opsin, which is a by-product of bleaching. As the function of the RPE and Bruch's membrane complex deteriorates, or is otherwise impaired, the photoreceptors suffer from a deficient supply of nutrients and reduced clearing of toxins and by-products of bleaching. This results in a reduction in the health and function of photoreceptors.
Rod photoreceptors are responsible for vision in dim light, while cone receptors allow for responses to bright light and colors. Rods are particularly vulnerable to the effects of reduced function of the RPE and Bruchs membrane complex and as such, this decay results in reduced scotopic, or dark-adapted vision
Dark-adaptation can be defined as the recovery of light sensitivity by the retina in the dark after exposure to a bright light (bleaching). As such, dark adaptation provides a useful assessment of the health of the RPE and/or Bruch's membrane complex.
Rod receptors seem to be effected by damage to the RPE and/or Bruch's membrane prior to serious deterioration of cone receptors. This is significant as the early detection of impaired dark adaptation could allow novel treatment options for a range of disease before the serious visual impairment associated with cone defects becomes apparent. As there are no treatment options currently available to reverse damage associated with most retinal diseases, providing treatment before damage is done, is crucial to a successful outcome.
The RPE complex slowly deteriorates with age, but accelerated deterioration is the major cause of early stage AMD. In most eyes, debris that is not cleared through the membrane complex builds up between the Bruch's membrane and the RPE to form drusen. Early or dry AMD progresses to wet AMD when this drusen causes inflammation that sets off a chain reaction resulting in the growth of many small blood vessels up into the RPE. These delicate vessels are prone to bursting, which causes blood to leak into the retina. Both the growth and the leaking blood causes severe damage to the retina and this is the stage of AMD that is most serious. Preventing progression to this stage and treating it when it does occur is the major target for currently marketed pharmaceuticals.
The measurement of dark adaption of the human eye has been known for some time. In more recent years, research has investigated abnormal dark adaption and found a high correlation with the presence of Age-related Macular Degeneration (AMD) and structural changes in the Bruch's membrane. Research has also found that dark adaption anomalies indicate the presence of AMD much earlier than other detectable irregularities.
A study in 2011 found rod recovery to be the best way to detect early AMD but because of the difficulties in measuring rod recovery they ranked it much lower than other techniques (Dimitrov, et al., “Visual function tests as potential biomarkers in age-related macular degeneration”; Invest. Ophthalmol. Vis. Sci., 2011, 9; 52(13):9457-69).
A 2012 study found that dark adaptation showed a strong ability to detect early functional changes that could lead to AMD, but becomes significantly poorer as a monitoring tool after the onset of AMD. Steady state tests such as flicker perimitry (14 Hz flicker) showed a continuous decline as eye function deteriorates and offer a better quality test of disease progression (Dimitrov, et al., “Relationship between clinical macular changes and retinal function in age-related macular degeneration”; Invest. Ophthalmol. Vis. Sci., 2012, 7; 53(9):5213-20).
The methods known in the prior art involve bleaching the retina of a subject with a bright light source and generating a stimulus with a specific spectrum and intensity to be seen by the subject. When the stimulus is seen the subject acknowledges this. The time delay from the time of bleaching to the time of stimulus and the level of intensity is recorded and further analysed to establish the physiological parameters characteristic for the disease. Multiple measurements of the stimulus point can be taken to increase accuracy of measurement.
A publication by Jackson & Edwards contains a description of a short duration dark adaptation protocol for assessment of age-related maculopathy (ARM) using a Dark Adaptometer called the AdaptDX (“A short-duration dark adaptation protocol for assessment of age-related maculopathy”; J. Ocul. Biol. Dis. Infor., 2008, 1:7-11). The AdaptDX presents a stimulus point at the line of sight. This publication notes that using the twenty minute procedure in combination with the AdaptDx dark adaptometer allows the differentiation of early AMD and normal patients. As the severity of AMD increases, rod recovery rate and rod intercept drop very quickly.
Another known device is based on retinal imaging overlaying the retinal image surface to a projected light pattern. A third apparatus uses a tilting mirror system to produce the stimulus point at desired position.
Improved methods and apparatuses to quickly and efficiently measure dark-adaptation in a patient are highly desirable.
The reference to any prior art in this specification is not, and should not be taken as, an acknowledgement or any form of suggestion that the prior art forms part of the common general knowledge.